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‘Sarah is a baby girl born by an emergency caesarean section following a period of observation for non-reassuring cardiotocographic recordings. She was initially ‘flat’ and received positive pressure ventilation for 3 min before establishing spontaneous breathing. Her Apgar scores were 1, 6 and 8 at 1, 5 and 10 min, respectively; cord pH was 7.08 and standard base excess (sBE) was −12.1. Sarah stayed with her mother as she was breathing normally and centrally pink despite being mildly hypotonic with minimal activity. At 10 hours of age, she started to develop recurrent seizures. Cerebral MRI showed extensive diffusion restriction patterns compatible with acute hypoxic–ischaemic insult.’ Sarah is a composite case, developed to include real events that we and others have observed. Unfortunately, many neonatal units receive similar cases every year and they often end up not offering therapeutic hypothermia, the only available treatment with proven safety and efficacy to this condition.1 The current guidelines are not inclusive and do not consider borderline cases.2 3 The simple question clinicians should ask themselves, is it unreasonable to treat a newborn with perinatal asphyxia and moderate encephalopathy? Babies, in a situation like Sarah, may lose the opportunity to be treated with therapeutic hypothermia because they miss a single criterion from the current cooling guidelines. The selection criteria in the initial randomised controlled trials of hypothermia were developed to identify the highest risk newborns who had been exposed to hypoxia–ischaemia. Newborns who had lower levels of risk were pragmatically excluded. Now that the evidence for benefit is well established,1 4 we propose that those entry points …

BACKGROUND A clinically significant patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in premature newborns. Symptomatic PDAs are often treated with prostaglandin synthesis inhibitors (PSI), but controversy remains if PSIs should also be used to manage early, asymptomatic PDAs. OBJECTIVE To systematically identify, critically appraise, and evaluate the efficacy and safety of pharmacological management of pre-symptomatic PDA in preterm newborns after confirmed patency by echocardiography. STUDY DESIGN Systematic review and meta-analysis. SEARCH METHODS We searched MEDLINE (Ovid), EMBASE (Ovid), Cochrane Central Register of Controlled Trials (Wiley), from date of inception to February 2017. Supplemental searching was performed in Scopus and Web of Science to identify additional relevant citations. We also searched conference proceedings, reference lists of relevant articles and the WHO International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA We included only randomized controlled trials (RCTs) that compared the use of indomethacin or ibuprofen to placebo for treatment of pre-symptomatic PDA in preterm newborns (

Objective To study the impact of cumulative exposure to hypoxemia on the development of retinopathy of prematurity (ROP) in preterm infants less than 29 weeks' gestation. Study Design This is a retrospective analysis of the effect of cumulative exposure to hypoxemia during the first 10 weeks of life in preterm infants Results Cumulative hypoxemia exposure was significantly associated with ROP requiring treatment. When adjusted for other neonatal morbidities, only gestation was consistently associated with ROP requiring treatment. Conclusion Cumulative exposure to hypoxemia in the first few weeks was not associated with ROP or treatment of ROP after adjustment for confounders.

The successful clinical translation of therapeutic hypothermia offers the tantalizing possibility that further improvements in outcomes may be possible by combining cooling with other neuroprotective drugs. The challenge now is to select from a daunting range of potential treatments. The patient's best interest must be central to ethical decision making at all times. However, the beneficence or nonmaleficence of potential therapies is seldom clear for any individual patient at the time of testing new therapies. Clinical randomized controlled trials are generally acknowledged by the scientific community as the ‘gold standard' for evaluating interventions in health care. Therefore, ethical trial design is of the utmost importance. This paper explores contrasting ethical perspectives on how to select new interventions to treat neonatal encephalopathy after perinatal hypoxia-ischemia.

From the Winnipeg Regional Health Authority, Winnipeg, Manitoba, Canada; 2 3 the standard of care for treating newborns with moderate to severe HIE. Therapeutic hypothermia has been found to reduce the risk of death or major neurodevelopmental disability at age 18 months (risk ratio [RR], 0.76; 95% CI, 0.69-0.84) and to increase survival with normal neurologic function (RR, 1.63; 95% CI, 1.36-1.95). Recent studies have confirmed improved neurocognitive outcomes at school age. Those studies involved predominantly developed countries. In contrast, a systematic review of 7 trials including 567 newborns from LMI countries, using mainly low-cost cooling techniques, did not show a significant reduction in neonatal mortality (RR, 0.74; 95% CI, 0.441.25). Although the point estimate is consistent with estimates from the developed world, the wide CI of that result means that a clinically important benefit or harm could not be excluded. Furthermore, there was insufficient long-term follow-up to allow assessment of whether hypothermia had improved neurodevelopmental outcomes. The heterogeneity of outcomes in studies from LMI countries may be an artifact of poorly designed studies, many of which were very small. The largest study in that review, which carried almost one-half of the weight in the primary outcome (neonatal mortality), may have introduced selection bias by including more boys (85%) and violated its protocol by including 20% cases with mild encephalopathy. Overall, 15% of the patients in these studies hadmild encephalopathy, and, consistent with this, only 12% required ventilation. Newborns with mild HIE have a low risk of mortality, reducing the study’s power and potentially leading to a false conclusion that the intervention is not conclusive when the intervention was not applied to the correct target population. It is unclear whether the low frequency of mechanical ventilation reflects only selection for milder cases, or whether resource limitations constrained care. Alternatively, the heterogeneity of outcomes potentially could be “real,” that is, related to medical factors that impair

Objective To establish the evidence of therapeutic hypothermia for newborns with hypoxic ischemic encephalopathy (HIE). Data Sources Cochrane Central Register of Controlled Trials, Oxford Database of Perinatal Trials, MEDLINE, EMBASE, and previous reviews. Study Selection Randomized controlled trials that compared therapeutic hypothermia to normothermia for newborns with HIE. Intervention Therapeutic hypothermia. Main Outcome Measures Death or major neurodevelopmental disability at 18 months. Results Seven trials including 1214 newborns were identified. Therapeutic hypothermia resulted in a reduction in the risk of death or major neurodevelopmental disability (risk ratio [RR], 0.76; 95% CI, 0.69-0.84) and increase in the rate of survival with normal neurological function (1.63; 1.36-1.95) at age 18 months. Hypothermia reduced the risk of death or major neurodevelopmental disability at age 18 months in newborns with moderate HIE (RR, 0.67; 95% CI, 0.56-0.81) and in newborns with severe HIE (0.83; 0.74-0.92). Both total body cooling and selective head cooling resulted in reduction in the risk of death or major neurodevelopmental disability (RR, 0.75; 95% CI, 0.66-0.85 and 0.77; 0.65-0.93, respectively). Conclusion Hypothermia improves survival and neurodevelopment in newborns with moderate to severe HIE. Total body cooling and selective head cooling are effective methods in treating newborns with HIE. Clinicians should consider offering therapeutic hypothermia as part of routine clinical care to these newborns.